Localized modulation of tissues and cells to enhance therapeutic effects including renal denervation

Active Publication Date: 2013-09-26
MERCATOR MEDSYST
View PDF8 Cites 34 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0048]Provided herein is a method for enhancing the uptake of therapeutic agents into tissue comprising modulating pH of the tissue by creating a zone of the tissue having a center and an outer edge, wherein the zone comprises a modulated pH as compared to a pre-modulation pH of the tissue prior to modulation or as compared to a neutral pH, wherein zone comprises a gradient of pH that is most modulated at the center of the zone and reduces to the pre-modulation pH of the tissue or to neutral pH at the outer edge of the zone, and wherein enhanced uptake of a therapeutic agent occurs in the zone as compared to uptake that would occur into tissue at the pre-modulation pH or at neutral pH.
[0049]Provided herein is a method for enhancing the uptake of therapeutic agents into tissue comprising—modulating pH of the tissue by creating a zone of the tissue having a

Problems solved by technology

While it has been published that pH differences may alter drug effects in cell culture assays, the localized or regionalized modi

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Localized modulation of tissues and cells to enhance therapeutic effects including renal denervation
  • Localized modulation of tissues and cells to enhance therapeutic effects including renal denervation
  • Localized modulation of tissues and cells to enhance therapeutic effects including renal denervation

Examples

Experimental program
Comparison scheme
Effect test

Example

Example 1

In Vitro Response of Nerve and Smooth Muscle Cells to pH and Guanethidine Monosulfate Concentration

[0173]Guanethidine Monosulfate and pH interaction studies were performed on sympathetic neuronal and perivascular and vascular cell types. The following cell types were examined:[0174]SH-SY5Y: Human neuroblastoma line SH-SY5Y, plated but uninduced[0175]Induced SH-SY5Y: SH-SY5Y induced with retinoic acid to differentiate into neurite growing sympathetic nerve cells[0176]rPC-12: Adherent-type rat PC-12 cells, plated but uninduced[0177]Induced rPC-12: PC-12 induced with NGF to differentiate into neurite growing sympathetic nerve cells[0178]Rat SCG: Primary rat superior cervical ganglia cells[0179]hAoSMC: Primary human aortic smooth muscle cells

[0180]Cells were treated with 0, 1, 10, 100 or 1000 μg / mL guanethidine monosulfate (GNT), or 10 μg / mL GNT and 17% IsoVUE370, at pH 6.3 and pH 9.3. At 4 h and in replicate cultures at 24 h, the medium was replaced with regular growth medium ...

Example

Example 2

Animal Study and Follow Up Studies

[0210]Guanethidine tested in certain preclinical studies showed that there was nerve damage, however the form of the guanethidine tested in these studies was guanethidine hemisulfate. Later testing in an animal study using guanethidine monosulfate at an unbuffered pH (6.3 or less) produced safe results, but failed to show significant denervation. Buffering of guanethidine monosulfate to a pH in the ranges successfully shown to denervate using guanethidine hemisulfate is possible. Titration experiments as shown in FIG. 20B depict how guanethidine monosulfate can be buffered with sodium hydroxide to achieve the same pH as the guanethidine hemisulfate used in the studies with successful denervation. This alkaline buffered form of guanethidine monosulfate may be used to denervate nerves by delivery of such composition to tissue surrounding such nerves. Such delivery may be transluminal, for example using devices noted herein, or may be delivere...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

PropertyMeasurementUnit
Fractionaaaaaaaaaa
Fractionaaaaaaaaaa
Fractionaaaaaaaaaa
Login to view more

Abstract

Pharmaceutical preparations, compositions, systems, and devices including medical devices and diagnostic or therapeutic agents, and methods to treat disease by modification of local tissue environment to modulate the therapeutic index of locally or systemically delivered therapeutic or diagnostic agents. Improved ability to reduce sympathetic nerve activity in the adventitia and perivascular tissues around arteries and veins in the body. Modulation of the local tissue environment around an artery to enable more effective denervation with or without a therapeutic agent. Modulation may include adjustment of the pH of the tissue.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims the benefit of U.S. Provisional Application No. 61 / 548,822, filed Oct. 19, 2011, which application is incorporated herein by reference in its entirety.BACKGROUND AND SUMMARY OF THE INVENTION[0002]Pharmaceutical and biotherapeutic agents interact with cells differently depending on the local physiologic conditions of the tissue in which they are delivered or taken up. For example, pH changes can lead to differences in the uptake of drugs into cells due to membrane permeability or polarization of the pharmaceutical agent, among other reasons.SUMMARY OF THE INVENTION[0003]While it has been published that pH differences may alter drug effects in cell culture assays, the localized or regionalized modification of pH within the body to enable more rapid drug uptake, more rapid clearance, or improved effect has not been attempted.[0004]Provided herein are compositions, methods, devices, and systems that generate this effec...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
IPC IPC(8): A61K31/395
CPCC07D295/13A61K31/395A61P11/00A61P25/00A61P25/02A61P29/00A61P5/50A61P9/04A61P9/12
Inventor SEWARD, KIRK P.
Owner MERCATOR MEDSYST
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap